The selective estrogen receptor modulator (SERM) tamoxifen (TAM) is the most widely prescribed endocrine therapy for the treatment and prevention of breast cancer. The development of resistance to TAM, either de novo or acquired, limits its clinical effectiveness, leading to disease progression. Before the introduction of TAM, breast cancer patients received high-dose 17β-estradiol (E2) or diethystilbesterol (DES) treatment. Although similar response rates were observed (9, 10), TAM treatment became the mainstay due to a lower incidence of side effects.
Protein kinase C α (PKCα) belongs to a family of serine/threonine protein kinases (1, 2). The expression of PKCα is associated with disease outcome for breast cancer patients on endocrine therapy. A shorter duration of response to endocrine therapy was associated with PKCα expression (3) and patients whose primary tumors overexpress PKCα were more likely to experience disease recurrence when treated with TAM (4). PKCα positivity is also associated with poor patient survival and breast cancer aggressiveness (5).